P511: RISK FACTORS AND INCIDENCE OF CARDIAC EVENTS IN A LARGE COHORT OF 525 ADULT PATIENTS WITH NEWLY DIAGNOSED NON-M3 ACUTE MYELOID LEUKEMIA
Authors: B. Boluda, A. Solana-Altabella, I. Cano, D. Martínez-Cuadrón, E. Acuña-Cruz, L. Torres-Miñana, R. Rodríguez-Veiga, D. Martínez-Campuzano, R. García-Ruiz, P. Lloret, P. Asensi, A. Serrano, A. Osa-Sáez, J. Agüero-Ramón-Llín, M. Rodríguez-Serrano, F. Buendía-Fuentes, J. E. Megías-Vericat, B. Martín-Herreros, E. Barragán, C. Sargas, M. Salas, M. Wooddell, C. Dharmani, M. A. Sanz, J. De La Rubia, P. Montesinos
Journal: HemaSphere (2022)

Background: The incidence of cardiac morbidity and mortality in acute myeloid leukemia (AML) population is not well known. AML patients (pts) receive potentially cardiotoxic drugs such as anthracyclines, QTc prolonging drugs such as FLT3 inhibitors, azoles, among others. Cardiac events can emerge in pts with previous cardiac diseases, or due to the toxicity of chemotherapy and other concomitant medications. So far, no previous studies have provided a holistic view of cardiac issues in a real-world series of AML pts. Aims: To estimate the cumulative incidence (CI) of cardiac events in a large series of unselected pts with AML in a single Spanish institution, and to identify risk factors associated with their development. Methods: Between January 2011 and June 2020, 571 pts were consecutively diagnosed with AML in Hospital La Fe, Valencia. The median follow-up of alive patients was 33 months. Clinical records were reviewed from diagnosis to death/last follow-up. Cardiac events were coded according to CTCAE. There were 525 treated pts, 285 (54%) with intensive chemotherapy and 240 (46%) with non-intensive therapy. Results: Among 46 untreated pts, 7 (15%) died due to cardiac events. Median age of 525 treated pts was 65 years, 331 (58%) male, and 73 (13.9%) had prior relevant cardiac comorbidities; 77 (14.7%) had FLT3-ITD mutation and 38 (7.2%) received front-line FLT3 inhibitors. Overall, 488 cardiac events were recorded, 19 (3.6%) pts had fatal cardiac events and 288 (54.9%) had any grade of non-fatal cardiac events. The 9-years CI of grade 1-2 QTcF prolongation was 11.2%, 2.7% pts had grade 3 QTcF prolongation >500ms, and no patient had grade 4 o 5. The 9-years CI of grade 1-2 cardiac failure was 1.3%, grade 3-4 15%, and grade 5 2.1%. The 9-years CI of grade 1-2 arrhythmia was 1.9%, grade 3-4 9.1%, and no pts had grade 5. Among 307 pts with cardiac events, 38 (12%) pts developed the first event before starting treatment, 132 (43%) during first cycle, 31 (10%) during consolidation, 55 (18%) during non-intensive further cycles, 14 (5%) during hematopoietic cell transplantation and 37 (12%) during follow-up. In the univariate analysis, pts with prior cardiac antecedents had increased incidence of fatal cardiac events compared with pts with no prior cardiac disease (CI at 9 years 20.1% vs 4.9%, p<0.001). Pts older than 65 years of age (64.4% vs 49.9%, p<0.001), prior cardiac disease (73% vs 54.6%, p=0.004) or included in clinical trial (65.2% vs 50.8%, p<0.001) had increased CI of non-fatal cardiac events. Multivariate analysis showed that prior cardiac disease was associated with increased incidence of fatal cardiac events [Hazard Ratio (HR) 1.9, p<0.001]. Age >65 (HR 2.2, p<0.001), prior cardiac disease (HR 1.4, p=0.02) and non-intensive chemotherapy (HR 1.8, p=0.004) were associated with increased CI of non-fatal cardiac event. Median overall survival (OS) in the overall cohort was 11.4 months (9.6-13.4 months, IC 95%). Among 285 intensive therapy pts, median OS was 22 months, 34 months in pts without cardiac events (n=125), 43 months with grade 1-2 (n=52), 15 months with grade 3-4 (n=98), and 5.2 months with grade 5 (n=10) (p<0.001). Image:Summary/Conclusion: We observed a high CI of cardiac events (58.5%) in a real-world series of patients undergoing AML therapy, associated with significant mortality due to cardiotoxicity (3.6%), and decreased OS. Prior history of cardiac comorbidity was associated with an increased risk of fatal cardiac events. Older age, cardiac comorbidities, and non-intensive therapies were related to non-fatal events.